The proposed research has two overall objectives, both of which will be approached through a study of the intra-axonal transport of proteins in neurons. The first objective is to elucidate fundamental neuronal processes (e.g., synapse formation, regeneration, trophic interactions, and the intra-axonal process itself) by studying the molecular events that mediate them. In particular, we will characterize individual intra-axonally transported proteins with respect to 1) their physical and chemical properties, 2) their mechanism of transport, 3) their location and function with neurons, and 4) their genetic and physiological regulation. By concentrating our attention upon the intra-axonally transported proteins (and in particular upon those whose transport is altered during important neuronal events such as regeneration), we hope to determine how the axonal and synaptic functions mediated by these proteins are accomplished and regulated. The second overall objective is to use the intra-axonal transport of proteins and an experimental model system for understanding the general principles of how cells move materials from one site to another. The maintenance of a cell's organization must depend upon its ability to translocate materials in an orderly way. Since the distances which must be traversed by newly synthesized materials in many neurons is much larger than in most other types of cells, the intra-axonal transport process in neurons should be an advantageous system for discovering general mechanisms of membrane and cell dynamics.